Connective Tissue Diseases Flashcards
What is Systemic Lupus Erythematous (SLE)
A chronic autoimmune (seropositive) disease that can affect almost any organ system, therefore presentation can be very variable
Autoantibodies associated with SLE
ANA (99% sensitive, but not specific)
Anti-DNA (70% sensitive, but 99% specific)
Anti-Sm (33% sensitive, 99% specific)
main organs/systems affected by SLE
skin joints kidneys blood cells nervous system
what type of hypersensitivity reaction is SLE
Type III (immune complex)
immunological response in SLE
Anti-DNA antibodies and ANA antibodies form immune complexes with antigens which are deposited in small vessels in skin, joints, kidneys, resulting in complement activation
what is the cause of SLE
largely unknown, but it is multifactorial
i.e. environmental insult in a genetically predisposed individual
is SLE more common in males or females?
Typical age of onset?
Females! >90%
age of onset 20s-30s
constitutional symptoms in SLE
fever
malaise
weight loss
MSK symptoms in SLE
arthralgia (joint pain)
myalgia (muscle pain)
inflammatory arthritis - non-erosive
increased prevalence of AVN esp. femoral head
Muco-cutaneous symptoms in SLE
malar butterfly rash photosensitivity discoid lupus subacute cutaneous lupus oral/nasal ulceration Raynaud's phenomenon sclerodactyly alopecia
Renal symptoms in SLE
lupus nephritis
persistent proteinuria
Respiratory symptoms in SLE
pleurisy pleural effusions pneumonitis pulmonary embolism pulmonary hypertension interstitial lung disease
Haematological symptoms in SLE
leukopenia
lymphopenia
anaemia
thrombocytopenia
Neurological symptoms in SLE
seizures
psychosis
headache
aseptic meningitis
Cardiac symptoms in SLE
pericarditis pericardial effusion pulmonary hypertension sterile endocarditis accelerated ischaemic heart disease
GI symptoms in SLE
autoimmune hepatitis
pancreatitis
mesenteric vasculitis
Ix for SLE
FBC - anaemia, leukopenia, thrombocytopenia
Immunology -
ANA - sensitive, but not specific. Take seriously if other markers are also positive
Anti-DNA - specific, but only +ve in 60%
Urinalysis -
glomerulonephritis
Imaging -
evidence of organ involvement
CT, MRI, echo
General approach to Tx of SLE
Depends on its manifestations
counselling, regular monitoring, avoidance of excessive sun exposure, pregnancy issues (often flares)
Tx of skin disease and arthralgia in SLE
- Hydroxychloroquine (DMARD)
- NSAIDs (naproxen) - for as short a period as poss
- Corticosteroids (pred)
Tx of SLE if there is inflammatory arthritis or organ involvement
- Immunosuppression (azothioprine)
- DMARDs
- Corticosteroids (pred)
Tx of SLE if there is lupus nephritis or CNS involvement
- Cyclophosphamide (alkylating chemo agent)
2. IV steroids
Tx of SLE in unresponsive cases
biologic therapy - Rituximab
IV immunoglobulins
How should SLE be monitored
Check anti-DsDNA antibodies and complement levels regularly
Check urinalysis for blood or protein
Cardio - BP and cholesterol
What is Sjogrens syndrome
Autoimmune seropositive condition that is characterised by lymphocytic infiltrates in exocrine glands
What is an exocrine gland
glands that produce and secrete substances onto an epithelial surface by way of a duct
What glands are usually affected in Sjogren’s syndrome
Lacrimal –> therefore dry eyes (keratonconjunctivitis sicca)
salivary –> therefore dry mouth (xerostomia)
Apart from dry eyes and mouth, what other symptoms can be present in Sjogrens syndrome
arthralgia fatigue vaginal dryness parotid gland swelling peripheral neuropathy interstitial lung disease
Autoantibodies associated with Sjogrens syndrome
Anti-Ro
Anti-La
Does Sjogren’s syndrome always occur on its own
No!
Can be primary Sjogren’s syndrome (no other conditions)
Or secondary Sjogren’s syndrome - to other autoimmune conditions e.g. RA, SLE
Test for ocular dryness in Sjogrens
Schirmer’s test
quantitative measure of tears. filter paper placed in lower conjunctival sac. test is +ve is <5mm of paper is wet after 5 mins.
Tx of Sjogren’s syndrome
Dry eyes - luricating eye drops
Dry mouth - artificial saliva, pilocarpine (cholinergic)
Arthralgia and fatigue - hydroxychloroquine
Severe systemic disease - immunosuppression
What is systemic sclerosis also known as
scleroderma
What is systemic sclerosis
a mulit-system seropositive autoimmune disease characterised by functional and structural abnormalities of small blood vessels, fibrosis of skin and internal organs.
2 main subtypes of systemic sclerosis & auto-antibodies associated with each
limited systemic sclerosis - anti-centromere antibody
diffuse systemic sclerosis - anti Scl-70 antibody
What is the difference between limited and diffuse systemic sclerosis
more rapid development of skin changes and earlier organ involvement in diffuse systemic sclerosis compared to limited systemic sclerosis
cutaneous presentations of systemic sclerosis
(skin eventually becomes thickened and tightened)
RAYNAUDS!!
centrally located skin sclerosis on arms, faces and/or neck
scerodactyly (thickening of skin in fingers and toes)
telangiectasia (red dots on the fingers, palms, face)
calcinosis (subcutaneous deposits of calcium in digits)
organ presentations of systemic sclerosis
pulmonary hypertension pulmonary fibrosis accelerated hypertension eventual renal crisis inflammatory arthritis myositis gut involvement - presents as dysphagia, malabsorption, bacterial overgrowth
pneumonic to remember presentation of limited systemic sclerosis
CREST syndrome
Calcinosis Raynaud's Esophageal & gut dysmotility Sclerodactyly Telangiectasia
Mx of renal crisis in scleroderma
- ACEi - lisinopril
- additional anti-hypertensives
- renal dialysis or transplant
Mx of raynaud’s in scleroderma with no digital ulceration
- CCB - amlodipine, nifedipine
2. aspiriin or Pentoxifylline
Mx of Raynauds in scleroderma with digital ulceration
- phosphodiesterase 5 inhibitor - sildenafil, bostentan
2. Iloprost
Mx of skin involvement in scleroderma
- topical immollient
pruritus - steroids
thickening - cyclophosphamide
Mx of GI involvement in scleroderma
PPI - omeprazole
Mx of interstitial lung disease in scleroderma
cyclophosphamide
what is Mixed Connective Tissue Disease (MCTD)
an overlap syndrome - a group of conditions that meets the classification criteria for more than 1 well recognised rheumatological disease
Features of MCTD
Raynauds Arthralgia/arthritis Myositis Sclerodactyly Pulmonary hypertension Interstitial lung disease
Auto-antibody associated with MCTD
Anti-RNP antibodies
What is anti-phospholipid syndrome
an autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss.
auto-antibodies associated with anti-phospholipid syndrome
Anticardiolipin antibodies
Lupus anticoagulant antibodies
pneumonic to remember anti-phospholipid syndrome
CLOT
Coagulation defect
Livedo reticularis
Obstetric (recurrent miscarriage)
Thrombocytopenia
What is the criteria for pregnancy loss in anti-phospholipid syndrome
Pregnancy loss with no other explanation 10-34/40 weeks or 3 pregnancy losses with no other explanation <10/40 weeks
What is livedo reticularis
Lace-like purplish discolouration of skin seen in anti-phospholipid syndrome
What valvular heart problem can be found in patients with Anti-Phospholipid syndrome
Sterile endocarditis –> Libman-Sacks endocarditis
embolisation can occur from these lesions
Tx of anti-phospholipid syndrome
initial anti-coagulation in acute thrombosis –> LMWH
then life-long warfarin
pregnancy - LMWH
do all patients with anti-phospholipid syndrome receive anti-coagulation
No - if they have it but have never had thrombosis, they don’t require anti-coagulation
What is gout
a crystal arthropathy caused by deposition of URATE crystals within a joint
what is uric acid
the final compound in the breakdown of purines in DNA metabolism (adenine and guanine).
How does hyperuricaemia occur to cause gout
increased urate production e.g.
inherited enzyme defects
psoriasis
alcohol
decreased renal urate excretion e.g. chronic renal impairment volume depletion e.g. heart failure hypothyroidism thiazide diuretics
most common joints affected by gout
first MTP joint
ankle
knee
presentation of gout
intense red hot swollen joint
symptoms last for 7-10 days if untreated then resolve
what are ‘gouty tophi’
painless white accumulation of uric acid which can occur in the soft tissues and occasionally erupt through the skin
Ix for gout
synovial fluid sample for polarising microscopy
- needle shaped crystal s
- negative birefringence
Tx acute gout
- NSAID
- Colchicine
- Corticosteroids
Prophylaxis for gout
Allopurinol (xanthine oxidase inhibitor)
What medication should NOT be given in acute gout
Allopurinol - can potentiate further flares
When should prophylaxis for gout be started
2 weeks after acute attack
Adverse effects of allopurinol
rash
azothioprine interaction
What is pseudogout
a crystal arthropathy caused by deposition of CALCIUM PYROPHOSPHATE crystals in a joint
What conditions are associated with pseudogout
hyperparathyroidism
amyloidosis
Ix of pseudogout
synovial fluid sample for polarising microscopy
- rhomboid shaped crystals
- positive birefringement
What is chondrocalcinosis
calcium pyrophosphate deposition in cartilage in the absence of acute inflammation
Tx of pseudogout
- NSAIDs
2. Intra-articular steroids
Prophylaxis for pseudogout
There is none!!
low levels of which complement are associated with developing SLE
C3 & C4 (C4a and C4b)
Drugs causing drug-induced lupus
procainamide (Na channel blocker)
hydralazine (anti-hypertensive)
presentation of drug induced lupus
arthralgia
myalgia
skin (malar rash) and pulmonary involvement (pleurisy)
ANA +ve in 100%, Anti-DNA -ve
radiological features of gout
joint effusion (early sign)
well-defined “punched out” lesions with sclerotic margins
preservation of joint space (not in late)
no periarticular osteopenia
soft tissue tophi
pathogenesis of SLE
cellular remnants containing nuclear material are transferred to lymphatic tissues.
They are presented to T cells which then stimulates B cells to produce autoantibodies. IgG antibodies attack DNA resulting in antigen-antibody complexes causing damage in various areas
pneumonic to remember the causes of gout
DART
Diuretics
Alcohol
Renal disease
Trauma
